Bone marrow nonneoplastic
Normal
General
Author: Dragos C. Luca, M.D.
Last author update: 1 September 2012
Last staff update: 13 December 2021
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Bone marrow nonneoplastic
Table of Contents
Definition / general | Diagrams / tables | Structure | Microenvironment | Hematopoietic stem cells (HSC) | Hematopoietic regulatory factors | Hematopoietic lineages | Microscopic (histologic) description | Microscopic (histologic) images | Additional referencesCite this page: Luca DC. General. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrownormalbonemarrow.html. Accessed April 20th, 2024.
Definition / general
- 3 - 6% of total body weight
- Major organ for hematopoiesis at birth; also primary and secondary lymphoid organ
- Hematopoiesis sites change from axial and radial skeleton in newborns to flat bones of central skeleton by mid teens
- Pluripotent stem cells develop into myeloid blasts (myeloblasts, monoblasts, erythroblasts and megakaryoblasts) or lymphoblasts
- Cells are in storage pools for 5 - 7 days, then to blood and then to tissues
- Estimated daily production rates to maintain homeostasis in adults: 50 - 100 x 109 neutrophils, 150 - 200 x 109 platelets and 150 - 200 x 109 erythrocytes
- Cellularity of 90 - 100% in the first years of life, then adult proportions of ~50% reached over a widely variable time interval
- High M:E ratio during the first 3 days of life, progressive decrease by the third week and adult level (3 - 4:1) at 1.5 - 3 years of age
- Lymphocytes predominate in the first 1.5 - 3 years; relatively numerous eosinophils in the first 3 months
- Iron stores are usually absent during the first year of life (exception - first month can have occasional iron stores), then increase progressively and reach adult levels by 5 - 6 years of life
Diagrams / tables
AFIP images
Hematopoietic cell differentiation
Images hosted on other servers:
Hematopoietic cell differentiation
Normal bone marrow differential in adults
Structure
- Highly organized meshwork of thin walled capillary - venous sinuses surrounded by extracellular matrix, encased by cortical bone and traversed by trabecular bone (J Clin Pathol 1992;45:645)
- Nutrient (medullary) artery ramifies through marrow space to supply medullary cavity; its arterioles branch into capillaries that are continuous with thin walled sinusoids (capillary - venous sinuses)
- Capillary - venous sinus (CVS, basic bone marrow structural unit): inner endothelial cells and outer adventitial reticular cells (phagocytic, can become lipocytes; also synthesize collagen, laminin, fibronectin and proteoglycans)
- All newly formed mature hematopoietic cells are released into capillary - venous sinus, then pass into the blood: transcellularly (via cytoplasm) for erythrocytes and granulocytes, or via megakaryocyte pseudopod extension and fragmentation for platelets
- Capillary - venous sinus coalesce into venules, then veins, carrying newly formed mature hematopoietic cells to the systemic circulation
- No lymphatic channels
- Topographic distribution: myeloid - peritrabecular, erythroid - central, megakaryocytes associated with sinus walls and lymphocytes throughout (no lymphoid follicles in infancy)
Microenvironment
- Also known as "hematopoietic inductive environment"
- Formed by the adventitial (stromal) cells and their products (extracellular matrix proteins, cytokines, inhibitory factors and adhesion molecules)
- Provides support for hematopoietic stem cell renewal and produces factors responsible for osteogenesis
- Heterogeneous cell population: fixed fibroblasts, macrophages and adipose cells
- Extracellular matrix: collagen, fibronectin, laminin, thrombospondin and proteoglycans
Hematopoietic stem cells (HSC)
- Cells with multilineage hematopoietic differentiation potential and sustained self renewal activity
- Detected by their ability to regenerate long term multilineage hematopoiesis in myeloablated recipients
- Very infrequent in the bone marrow: 0.01 - 0.05% of mononuclear cells
- Defined via functional rather than morphologic characteristics: ability to undergo self renewal and produce multilineage progeny
- Express CD34, various cytokine receptors / adhesion molecules / extracellular matrix protein receptors (SCF, bFGF, IL11 / 3 / 1 / 6, GM-CSF, etc.)
- Endothelial cells likely have major role in regulation of trafficking and homing of hematopoietic stem cells within the bone marrow
- Immunophenotype: CD34+, Thy1+, c-kit+, Rhodamine 123 low, Lin-, CD45RO+, CD38-, flt+ and adhesion molecules
- Spectrum of evolution / maturation: hematopoietic stem cells → progenitor cell with multilineage commitment → progenitor cell with single lineage commitment → blast cell → mature cell
- Developmental continuum: progressive loss of proliferative capacity and gradual acquisition of specific lineage characteristics
Hematopoietic regulatory factors
- Cytokines produced by T lymphocytes, the monocyte - macrophage lineage and other bone marrow stromal cells (either inducers or inhibitors)
- Stimulatory cytokines (inducers): stem cell factor (SCF), colony stimulating factors (CSFs) and various interleukins (IL)
- Inhibitory cytokines: tumor necrosis factor beta (TNF-β), transforming growth factor alpha (TGF-α) and macrophage inflammatory protein 1alpha (MIP-1α)
- Some factors may be pleiotropic (positive or negative effect): TGF-β
Hematopoietic lineages
- Myeloid - monocytic: predominant in the bone marrow, progeny includes neutrophils (most numerous), eosinophils, basophils, monocytes / macrophages, dendritic cells and mast cells
- Other: erythroid, megakaryocytic, lymphoid, natural killer and osteoclasts
Microscopic (histologic) description
- Bone marrow biopsy: arterioles, venules, capillaries, sinusoids, adipose tissue, connective tissue and hematopoietic cells; mitotically active cells are usually paratrabecular and perivascular
- Bone marrow aspirate: hematopoietic cells (myeloid, erythroid, megakaryocytic, lymphoid), plasma cells (rare in infants), osteoblasts (most common in infants), osteoclasts, occasional adipocytes, endothelial cells or capillaries
Microscopic (histologic) images
Images hosted on other servers:
Bone marrow biopsy:
Normal marrow
Bone marrow aspirate smear:
Normal
Additional references
